An important association between circulating blood volume and renal excretion of sodium and water is well known. The renal handling of sodium can be considered to consist of two phases: a postprandial phase involved with the elimination of excess ingested sodium and a postabsorptive phase during which there is additional excretion of sodium, but at a markedly reduced rate. The major physiological requirement of this postabsorptive phase becomes the required reabsorption of filtered sodium from the renal tubules to prevent the dissipation of sodium stores. The central working hypothesis for the proposed studies is that the atrial natriuretic factor (ANF) endocrine system functions primarily as a postprandial mechanism to increase the renal excretion of excess ingested sodium and fluid, whereas the renin-angiotensin-aldosterone system functions predominantly during the postabsorptive interval to promote the reabsorption of filtered sodium from the renal tubules and reduce urinary sodium excretion. Thus, hormonal adjustments of renal sodium excretion for blood volume and pressure regulation must involve the temporal integration of these two endocrine feedback systems. It is reasonable to expect that pathophysiological changes in sodium-fluid volume homeostasis may involve alterations in postprandial or postabsorptive hormonal mechanisms, either separately or collectively. Specific Aim #1: To probe the ANF endocrine system following volume expansion produced by chronic mineralocorticoid excess. Two closely related hypotheses will be tested. It is hypothesized that: 1) enhanced postprandial stimulation of ANF secretion occurs and augments natriuresis int he volume-expanded animals following "escape" from chronic mineralocorticoid excess, and 2) enhanced renal responsiveness to circulating ANF occurs in these volume-expanded animals following "escape" from chronic mineralocorticoid excess. Specific Aim #2: To probe the endocrine pathophysiological mechanisms that potentially contribute to renal salt and water retention and edema formation in an animal model of high-output heart failure. Experimental animal models of heart failure demonstrate an enhanced sensitivity to aldosterone excess and a reduced capacity to "escape" from the sodium- retaining effects of the steroid. Experimental heart failure also is characterized by a blunted natriuretic response to circulating ANF. Two specific hypotheses will be tested. It is hypothesized that: 1) the reduced capacity to "escape" from chronic mineralocorticoid excess in experimental heart failure is related to a reduced postprandial capacity for the secretion of appropriate amounts of ANF in response to an ingested sodium load, and 2) the blunted natriuresis to transduction mechanism. Experiments will involve integrative whole animal studies with measurements of cardiovascular and endocrine parameters, urinary excretion of cGMP, renal function, and sodium balance. The proposed studies will be performed to produce experimental high-output heart failure.